Congratulations to NRU senior researcher Anjali Sankar for receiving an early career award (140.000 USD) from the American Foundation for Suicide Prevention for her project entitled 'Identifying neurobiological targets for suicide prevention in mood disorder'.

Suicide is a major public health concern, and mood disorders (MDs) such as major depression and bipolar disordersignificantly elevate the risk of suicidal thoughts and behaviors (STBs). Thus, there is an urgent need for identifyingobjective and modifiable targets for suicide prevention in individuals with MDs. The proposed AFSP Early CareerResearch Grant aims to identify brain-based features that are predictive of future suicidal behavior in individuals with MDs—features that can be targeted with new intervention and prevention strategies.

Existing cross-sectional studies reveal functional connectivity disturbances in the ventral prefrontal cortex (vPFC)and its connection sites in suicidal behavior. However, the notably scarce longitudinal studies and the small samplesizes have limited our understanding of whether these features also pertain to future suicide risk and how clinicaland behavioral factors interact with imaging markers to amplify suicide risk. Additionally, evidence suggests synapticconnection alterations in the vPFC in suicidal pathology, however much of that evidence has come from post-mortemstudies.

Therefore, to address these limitations, this project proposes two aims. The first aim is a longitudinal study to identifya functional connectivity model that can predict future suicidal behavior in MDs. The study examines functionalconnectivity measures in a Danish cohort (n=1000) for whom information on future suicidal behavior is availableusing the unique National Health Registers. The model is subsequently validated using an independent sample(n=200) from Yale University with longitudinal data on suicidal behavior. We will explore demographic, clinical,behavioral and psychosocial factors that interact with the brain imaging markers to amplify suicide risk. The secondaim represents a shift from post-mortem investigations of synaptic density in suicidal behavior. It utilizes the recentlydeveloped [11C]UCB-J radioligand for one of the first examinations of synaptic density in suicidal behavior in livingindividuals with MDs and examine its link to functional connectivity features.

This study has the potential to uncover novel targets for suicide risk reduction. The identification of replicableconnectivity features predictive of future suicidal attempts could point to targets that could be modifiable withneuromodulation techniques. Additionally, exploring the role of synaptic connection alterations in suicidal behavioroffers potential mechanisms for reducing suicide risk. This study represents a cornerstone for establishing aninternational research program dedicated to the study and prevention of STBs, and the findings could contribute todrug discovery and policy change for suicide prevention. It is planned that future studies will build on this one toinvestigate individuals with other psychiatric conditions to identify transdiagnostic aspects of risk and generalizabletargets for suicide prevention.